Our people's latest grants and accolades of 2016

20 December 2016
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Grants

Synaptic Function Research Group

Dr Chantelle Fourie

Neurological Foundation Philip Wrightson Postdoctoral Fellowship

$169,975

Interneuron networks underlying hippocampal plasticity and spatial learning and memory retrieval.

The role of the brain’s synaptic networks in controlling plasticity and memory

Chantelle’s research aims to uncover the role of hippocampal inhibitory synaptic networks in controlling synaptic plasticity and memory. This will provide new insights into the brain networks underlying memory and uncover novel targets for intervention to improve learning and memory, especially in neurological disease.

Dr Fourie will undertake her Neurological Foundation Philip Wrightson Postdoctoral Fellowship at Nanyang Technological University in Singapore under the supervision of Professor George Augustine.

This fellowship will enable Dr Fourie to expand her expertise in inhibitory networks and investigate their role in long-term plasticity and learning behaviour, by mastering and applying the latest in vitro and in vivo optogenetic techniques.

 

Associate Professor Johanna Montgomery 

Neurological Foundation Research Grant

$11,920

Can increased maternal dietary zinc prevent the development of autism-associated behaviours?

Associate Professor Montgomery’s data show that zinc increases brain cell communication, so zinc could be a target treatment strategy for ASD.

This study aims to determine whether increased dietary zinc during pregnancy and lactation can prevent the development of ASD behaviours in a mouse model of ASD, and whether this is associated with changes in synapses.

Together, the data will characterise, from synapse to behaviour, the potential of dietary zinc in ASD during brain development.

 

Dr Juliette Cheyne

Marsden Grant

$300,000

Measuring in vivo activity in the prefrontal cortex and its link to Autism Spectrum Disorders 

Autism Spectrum Disorders (ASD) are developmental disorders defined by learning difficulties, social deficits, sensory changes and stereotyped behaviours. In the brain, the prefrontal cortex (PFC) plays a major role in these higher level functions, and we hypothesise that the neuronal wiring in the PFC develops incorrectly in ASD.

We will utilise state-of-the-art in vivo cellular recording techniques to measure how network activity is altered during development of the PFC in ASD mice. In addition, we will determine how this affects sensory processing later in life by recording sensory-evoked activity in awake mice.

As spontaneous and sensory-driven activity both play key roles in developing neuronal connectivity, we will also examine whether altering sensory experience, by depriving mice of sensory input, affects network function similarly in wildtype and ASD mice.

By directly linking sensory stimulation with recordings of neuronal activity, this work will determine how observed activity changes in vivo could underpin ASD-related impairments in high-level sensory processing and behaviour that are mediated by the PFC. 

 

NeuroImmune Interactions Research Group

Akshata Achan, PhD candidate

Neurological Foundation Gillespie Postgraduate Scholarship

$104,499

How do melanoma cancer cells migrate into the brain and survive by avoiding our defensive immune system? 

Akshata’s research aims to investigate human melanoma cells to discover the key components that allow them to 1: migrate into the brain and 2: survive within the brain by avoiding our defensive immune system. Akshata hopes to follow this study by researching ways to block these processes.

 

Dr Scott Graham

Neurological Foundation Project Grant

$12,000

Which inhibitory immune checkpoint control proteins are expressed in human brain tumours?

Investigating a target for treatment of aggressive brain tumours

There is a clear and present need for better treatments for brain cancers. Immune “checkpoints” critically govern many aspects of our immune response to tumour cells, and are key regulators of T-cell activation, proliferation and function.

T-cells are a subtype of white blood cells which play a key role in the immune system and in fighting cancer. Immunotherapies targeting the immune-checkpoint control axis are proving to be the greatest breakthrough for advanced melanoma and several other types of aggressive cancer. These molecules offer incredible potential in brain cancer to suppress the tumour cells or switch on the correct T cell responses.

First however, we must understand the repertoire of their expression in brain tumours and identify those that represent the best targets; this is the aim of Dr Graham’s research project. 

 

Neural Reprogramming and Repair Laboratory

Nicole Edwards, Master's degree student

Neurological Foundation W & B Miller Postgraduate Scholarship

$104,499

Modelling the neurodevelopmental disorder Fragile X Syndrome by Direct Reprogramming

Developing an authentic research model of Fragile X Syndrome using an innovative New Zealand-developed technology

Fragile X Syndrome (FXS) is the most common genetic cause of intellectual disability and autism, and has been linked to impaired neuronal development and function.

To overcome the lack of access to live developing human neurons, Nicole’s supervisor, Associate Professor Bronwen Connor, has developed a strategy to generate immature brain cells directly from adult human skin through a technique called direct reprogramming.

Nicole’s postgraduate work will use this technique to generate immature brain cells directly from FXS patients to investigate changes in the expression of genes and proteins important for neuronal development and function. This project will establish a human model of FXS and progress the understanding of this disorder.

 

Molecular, Cellular and Network Neurophysiology

Professor Janusz Lipski

Principal Investigator

and

Professor Brian Hyland

Associate Investigator

Department of Physiology, University of Otago

Neurological Foundation Research Grant

$168,760

Preclinical efficacy of Uptake-2 blockers in augmenting dopamine production from levodopa: implications for treatment of Parkinson’s disease

Investigating the potential improvement of the effectiveness of a Parkinson’s disease drug by inhibiting a mechanism in a rat brain model

Professor Lipski’s study aims to improve the effectiveness of levodopa treatment in Parkinson’s disease, by inhibiting a recently discovered mechanism which inactivates dopamine.

If successful, this strategy will inform clinical administration of levodopa doses with the aim of using lower doses for a longer period of time, hopefully minimising the occurrence of side-effects while maintaining therapeutic effectiveness of the drug.

Professor Lipski’s ultimate goal is to reduce the suffering and improve quality of life of those affected by Parkinson’s disease.

 

Professor Janusz Lipski and Dr Peter Freestone

AMRF Project Grant

$150,019

Regulation of dopamine release by endocannabinoids

The current study will use advanced dopamine-detection (electrochemistry) and cell-type specific stimulation (optogenetics) techniques that are ideally suited to studying the complex network underlying dopamine release.

These approaches will establish the mechanism by which NADA controls dopamine levels and related movement behaviours.

A range of experimental models from living brain slices to freely moving animals will be used to provide a robust translational investigation.

The findings will determine whether the NADA-based mechanism is a suitable target for new therapeutic strategies for diseases like Parkinson’s disease

 

Developmental Brain Injury and Glial Cell Biology

Dr Rashi Karunasinghe

Neurological Foundation Wrightson Postdoctoral Fellowship

$180,629

Filling in the gaps in the brain: the developmental roles of extracellular hyaluronan in neuronal signalling and plasticity

The role of a molecular sugar in brain development 

Rashi’s preliminary research findings indicate intriguing roles for an extracellular matrix sugar called hyaluronan.

 This project will follow how neurons regulate hyaluronan levels in order to modify their molecular, structural, and electrophysiological properties during brain development.  

 

Dr Justin Dean

Neurological Foundation Research Grant

$11,788

Promoting myelination for functional recovery after subcortical white matter stroke – development of an endothelin-1 animal model

Investigating a specific pathway in the brain involved in movement recovery after stroke using a rat model

This project will establish an animal model to investigate the mechanisms of recovery along this pathway in the brain. This will allow Justin’s research team, to identify novel therapeutic targets which may raise the recovery ceiling above 70%.

 

Functional Neuroimaging

Dr David Moreau

Neurological Foundation Research Grant

$11,640 

Enhancing cognition: brain networks underlying effective training interventions

A pilot study to test a training intervention paradigm for cognitive improvements in children with neurodevelopmental disorders   

Dr Moreau and colleagues have developed a training intervention that has the potential to alleviate some of the negative effects of neurodevelopmental disorders. This initiative places the culmination of decades of research at the service of remediation.

While typical interventions targeting learning disorders come at it from a single angle, Dr Moreau and his team are tackling this problem on multiple fronts. Their unique approach combines a blend of exercise with a software regimen tailored to each individual.

Ultimately, this work could also impact remediation of the injured and ageing brain, paving the way for novel therapeutic interventions.

 

Clinical Neuroscience Laboratory

Associate Professor Cathy Stinear

Neurological Foundation Research Grant

$115,056

Spontaneous recovery of sensorimotor impairment after stroke

Recovery of movement and sensation after stroke – the 70% rule 

Clinical neuroscientist Associate Professor Cathy Stinear and colleagues Professors Alan Barber and Winston Byblow recently made the remarkable discovery that patients routinely recover 70% of the movement they have lost after stroke.

This 70% rule applies to all patients, provided a key pathway in the brain is preserved, regardless of their age or how much therapy they complete. This suggests that a fundamental biological process is at work, which is yet to be identified. In this study, Associate Professor Stinear and co-investigators Professors Barber and Byblow will use neurophysiology and neuroimaging techniques to explore the processes underlying the 70% rule.

The team will also be the first to study the recovery of sensory function, to see whether it also follows the 70% rule. Understanding the processes responsible for spontaneous recovery will identify new therapeutic targets to improve recovery after stroke.

 

Human Brain Plasticity and Neurodegenerative Diseases Group

Eli Shaul

The C and N Anderson Summer Studentship (Neurological Foundation)

$6,000

Optimising lipid antibodies to assess changes in Alzheimer’s disease hippocampus

Identifying the involvement of lipids in Alzheimer’s disease

In this project Eli will optimise a new method of detecting lipid changes in the brain that will allow correlation between other technological techniques that also detect lipid changes.

The overall aim is to understand which lipids are affected in AD as a first step to manipulating them to better treat Alzheimer’s disease.

 

The Vision and Attention Lab

Associate Professor Tony Lambert

Marsden Fund Grant

$675,000

Sight unseen: penetrating the enigma of unconscious vision.

Intriguingly, visual processing in the brain involves both an unconscious, and a conscious pathway. Therefore, conventional assessment methods, in which participants report what can be seen consciously, provide an incomplete picture of visual function.

This project will test predictions derived from our theory that the unconscious pathway guides eye movements, and develop a technique that assesses unconscious vision by measuring eye movements.

This technique will enable direct comparisons to be made between unconscious vision and conscious vision.

Our approach will lead to a more complete understanding of vision, and enable more comprehensive assessments of visual function to be undertaken.

 

The Neuropsychopharmacology Group

Rachael Sumner – PhD candidate

AMRF Doctoral Scholarship

$87,000

Cortical excitation – inhibition balance in health and disease

The main aim of this research is to investigate the use of electroencephalography (EEG) to measure biomarkers of cortical excitation/inhibition and neural plasticity in depression.

Reduced neural plasticity has been implicated in a number of brain based disorders, including depression. By targeting visual and auditory evoked neural activity this project will explore how measuring changes in sensory neural plasticity could be used as biomarkers of general brain health in depression.

 

Human Neurodegeneration Lab and Human Brain Plasticity and Neurodegenerative Diseases Group

Professor Mike Dragunow and Associate Professor Maurice Curtis

Dr Clinton Turner

AMRF Project Grant

$10,432

The prognostic significance of immune cell infiltrates in meningioma 

The goal of this research is to examine whether the composition and density of the immune cell infiltrate in meningioma is prognostically significant in predicting tumour recurrence.

This will potentially help improve the ability of the pathologist to predict tumour behaviour for an individual patient. It may also open up further research avenues into immune-modifying therapies in meningioma.

 

Clinical Visual Neuroscience Laboratory

Professor Steven Dakin

Cure Kids Innovation Seed Fund

$47,000

Using children’s eye movements to diagnose characterize and treat autism spectrum disorder

Autism spectrum disorder (ASD) is a developmental condition affecting 1/68 children in New Zealand. Early diagnosis of ASD is complicated by the fact that the condition can manifest in different ways.

 In this project we compare fixation-patterns (i.e. where children look) of typically developing children and children with ASD, when viewing commercial movies.

Our project is unusual in that we have developed a system for comparing fixation to the content of movies (based on labels attached to faces, objects etc.).

Results will allow us to determine two things. First, if such differences could contribute to the early diagnosis of ASD, Second, what is it about movies that drive differences (e.g. do children specifically avoid looking at speaking faces?).

 

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Awards

Neural Reprogramming and Repair Laboratory

Amy Chapman, PhD candidate

Amy is a completing the 3rd year of her PhD and is a Neurological Foundation PhD Millar Scholar.

Her paper “Rat Brain Sagittal Organotypic Slice Cultures as an Ex Vivo Dopamine Cell Loss System” has been accepted for publication in the Journal of Neuroscience Methods.

This paper described methods Amy established which allow her to generate a 3 dimension culture model of the whole rat brain.

Using this model, Amy demonstrated she could mimic the loss of cells and fibre pathways seen in Parkinson’s disease, and keep the cultures alive for up to 6 weeks. This has not been achieved before, and will provide a vital tool for studying cell replacement therapy to treat Parkinson’s disease

Amy has also won the Australasian Society for Stem Cell Research Young Investigator of 2016 Prize for her research entitled “Investigating the functional maturation of human induced neural precursor-derived neurons” at the 9th Annual meeting in Perth, 4-7 December.

Amy’s research is focused on the direct reprogramming of adult human skin cells to brain stem cells, and subsequently to mature neurons. She has developed novel methods by which to promote the survival and maturation of reprogrammed neurons. This research is key for both cell replacement therapy and for the use of live human neurons to model neurological diseases.

 

Rebecca Playne, PhD candidate

Rebecca is completing the 4th year of her PhD (submission in Feb 2017) and is a Neurological Foundation PhD Millar Scholar.

Her review “Understanding Parkinson’s disease through the use of cell reprogramming.” has been accepted for publication in Stem Cell Reviews and Research.

This review provides a unique summary of the field of cell reprogramming to model Parkinson’s disease which has been the basis of Rebecca’s PhD research.